Fronto-parietal coupling of brain rhythms in mild cognitive impairment: a multicentric EEG study

Electroencephalographic (EEG) data were recorded in 69 normal elderly (Nold), 88 mild cognitive impairment (MCI), and 109 mild Alzheimer's disease (AD) subjects at rest condition, to test whether the fronto-parietal coupling of EEG rhythms is in line with the hypothesis that MCI can be considered as a pre-clinical stage of the disease at group level. Functional coupling was estimated by synchronization likelihood of Laplacian-transformed EEG data at electrode pairs, which accounts for linear and non-linear components of that coupling. Cortical rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz). Compared to the Nold subjects, the AD patients presented a marked reduction of the synchronization likelihood (delta to gamma) at both fronto-parietal and inter-hemispherical (delta to beta 2) electrodes. As a main result, alpha 1 synchronization likelihood progressively decreased across Nold, MCI, and mild AD subjects at midline (Fz-Pz) and right (F4-P4) fronto-parietal electrodes. The same was true for the delta synchronization likelihood at right fronto-parietal electrodes (F4-P4). For these EEG bands, the synchronization likelihood correlated with global cognitive status as measured by the Mini Mental State Evaluation. The present results suggest that at group level, fronto-parietal coupling of the delta and alpha rhythms progressively becomes abnormal though MCI and mild AD. Future longitudinal research should evaluate whether the present EEG approach is able to predict the cognitive decline in individual MCI subjects.     

Reactivity of cortical alpha rhythms to eye opening in mild cognitive impairment and Alzheimer's disease: an EEG study

Cortical sources of resting eyes-closed alpha rhythms are typically abnormal in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects. Here we tested the hypothesis of a progressive impairment of cortical alpha reactivity to eye-opening across amnesic MCI and mild AD subjects, reflecting another aspect of the impairment of cortical neural synchronization. Resting electroencephalography (EEG) data were recorded in 36 normal elderly subjects (Nold), 91 amnesic MCI, and 31 mild AD subjects during eyes-closed and -open conditions. EEG sources were estimated by LORETA software. In the eye-closed condition, posterior alpha 1 (8-10.5 Hz) sources were lower in MCI and AD than Nold subjects. The opposite was true for occipital delta sources (2-4 Hz). Reactivity to the eyes-open condition showed posterior alpha 1 and alpha 2 (10.5-13 Hz) sources was high in the Nold, intermediate in the MCI, and low in the AD subjects. Furthermore, occipital alpha 1 reactivity across MCI and AD subjects was correlated to the cognitive impairment as revealed by Mini-Mental State Examination score. In conclusion, at least at group level, the continuum across amnesic MCI and mild AD status is related to an impaired reactivity of cortical neuronal synchronization to eyes opening at alpha rhythms.     

Resting state cortical electroencephalographic rhythms are related to gray matter volume in subjects with mild cognitive impairment and Alzheimer's disease

Cortical gray matter volume and resting state cortical electroencephalographic rhythms are typically abnormal in subjects with amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Here we tested the hypothesis that in amnesic MCI and AD subjects, abnormalities of EEG rhythms are a functional reflection of cortical atrophy across the disease. Eyes‐closed resting state EEG data were recorded in 57 healthy elderly (Nold), 102 amnesic MCI, and 108 AD patients. Cortical gray matter volume was indexed by magnetic resonance imaging recorded in the MCI and AD subjects according to Alzheimer's disease neuroimaging initiative project ( http://www.adni‐info.org/ ). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha1 (8–10.5 Hz), alpha2 (10.5–13 Hz), beta1 (13–20 Hz), beta2 (20–30 Hz), and gamma (30–40 Hz). These rhythms were indexed by LORETA. Compared with the Nold, the MCI showed a decrease in amplitude of alpha 1 sources. With respect to the Nold and MCI, the AD showed an amplitude increase of delta sources, along with a strong amplitude reduction of alpha 1 sources. In the MCI and AD subjects as a whole group, the lower the cortical gray matter volume, the higher the delta sources, the lower the alpha 1 sources. The better the score to cognitive tests the higher the gray matter volume, the lower the pathological delta sources, and the higher the alpha sources. These results suggest that in amnesic MCI and AD subjects, abnormalities of resting state cortical EEG rhythms are not epiphenomena but are strictly related to neurodegeneration (atrophy of cortical gray matter) and cognition. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Resting state cortical electroencephalographic rhythms and white matter vascular lesions in subjects with Alzheimer's disease: an Italian multicenter study

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.     

White-matter vascular lesions correlate with alpha EEG sources in mild cognitive impairment

It is an open issue if vascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI), as a preclinical stage of Alzheimer's disease (AD) at group level. In the present study, we tested the hypothesis that electroencephalographic (EEG) alpha rhythms, which are affected (i.e. decreased in amplitude) by AD processes, are relatively preserved in MCI subjects in whom the cognitive decline is mainly explained by white-matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold), 80 MCI, and 40 AD subjects. In the MCI subjects, white-matter vascular load was quantified based on MRI (0-30 Wahlund visual rating scale). EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), and beta 2 (20-30Hz). Low resolution electromagnetic source tomography (LORETA) was used for EEG source analysis. As expected, we observed that alpha 1 sources in parietal, occipital, and temporal areas were lower in amplitude in the AD and MCI subjects than in the Nold subjects, whereas the amplitude of wide delta sources was higher in the AD than in the Nold and MCI subjects. As novel results, the amplitude of parietal, occipital, and temporal alpha 1 sources was higher in the MCI V+ (high vascular load; N=42; MMSE=26) than MCI V- group (low vascular load; N=37; MMSE=26.7). Furthermore, a weak but significant (p<0.05) positive statistical correlation was found between the parietal alpha 1 sources and the score of Wahlund scale across all MCI subjects (i.e. the more severe white-matter lesions, the higher parietal alpha source power). The present results are in line with the additive model of cognitive impairment postulating that this arises as the sum of neurodegenerative and cerebrovascular lesions.     

Frontal white matter volume and delta EEG sources negatively correlate in awake subjects with mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz) has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A, Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study. Am J Neuroradiol. 2003 24(3):481-487]. In this study, we tested the hypothesis that such a relationship does exist not only in AD patients but also across the continuum of subjects with mild cognitive impairment (MCI) and AD. METHODS: Resting, eyes-closed EEG data were recorded in 34 MCI and 65 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. Cortical EEG sources were correlated with MR-based measurements of lobar brain volume (white and gray matter). RESULTS: A negative correlation was observed between the frontal white matter and the amplitude of frontal delta sources (2-4 Hz) across MCI and AD subjects. CONCLUSIONS: These results confirmed for the first time the hypothesis that the sources of resting delta rhythms (2-4 Hz) are correlated with lobar brain volume across MCI and AD subjects. SIGNIFICANCE: The present findings support, at least at group level, the 'transition hypothesis' of brain structural and functional continuity between MCI and AD.     

Resting EEG sources correlate with attentional span in mild cognitive impairment and Alzheimer's disease

Previous evidence has shown that resting delta and alpha electroencephalographic (EEG) rhythms are abnormal in patients with Alzheimer's disease (AD) and its potential preclinical stage (mild cognitive impairment, MCI). Here, we tested the hypothesis that these EEG rhythms are correlated with memory and attention in the continuum across MCI and AD. Resting eyes-closed EEG data were recorded in 34 MCI and 53 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). These sources were correlated with neuropsychological measures such as Rey list immediate recall (word short-term memory), Rey list delayed recall (word medium-term memory), Digit span forward (immediate memory for digits probing focused attention), and Corsi span forward (visuo-spatial immediate memory probing focused attention). A statistically significant negative correlation (Bonferroni corrected, P < 0.05) was observed between Corsi span forward score and amplitude of occipital or temporal delta sources across MCI and AD subjects. Furthermore, a positive correlation was shown between Digit span forward score and occipital alpha 1 sources (Bonferroni corrected, P < 0.05). These results suggest that cortical sources of resting delta and alpha rhythms correlate with neuropsychological measures of immediate memory based on focused attention in the continuum of MCI and AD subjects.     

Free copper and resting temporal EEG rhythms correlate across healthy, mild cognitive impairment, and Alzheimer's disease subjects.

OBJECTIVE: The present study tested the hypothesis that the serum copper abnormalities were correlated with alterations of resting electroencephalographic (EEG) rhythms across the continuum of healthy elderly (Hold), mild cognitive impairment (MCI), and AD subjects. METHODS: Resting eyes-closed EEG rhythms delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz), estimated by LORETA, were recorded in 17 Hold, 19 MCI, 27 AD- (MMSE< or =20), and 27 AD+ (MMSE20) individuals and correlated with copper biological variables. RESULTS: Across the continuum of Hold, MCI and AD subjects, alpha sources in parietal, occipital, and temporal areas were decreased, while the magnitude of the delta and theta EEG sources in parietal, occipital, and temporal areas was increased. The fraction of serum copper unbound to ceruloplasmin positively correlated with temporal and frontal delta sources, regardless of the effects of age, gender, and education. CONCLUSIONS: These results sustain the hypothesis of a toxic component of serum copper that is correlated with functional loss of AD, as revealed by EEG indexes. SIGNIFICANCE: The present study represents the first demonstration that the fraction of serum copper unbound to ceruloplasmin is correlated with cortical delta rhythms across Hold, MCI, and AD subjects, thus unveiling possible relationships among the biological parameter, advanced neurodegenerative processes, and synchronization mechanisms regulating the relative amplitude of selective EEG rhythms.     

Apolipoprotein E and alpha brain rhythms in mild cognitive impairment: a multicentric electroencephalogram study

OBJECTIVE: Relationships between the apolipoprotein E epsilon4 allele and electroencephalographic (EEG) rhythmicity have been demonstrated in Alzheimer's disease (AD) patients but not in the preclinical stage prodromic to it, namely, mild cognitive impairment (MCI). The present multicentric EEG study tested the hypothesis that presence of epsilon4 affects sources of resting EEG rhythms in both MCI and AD subjects. METHODS: We enrolled 89 MCI subjects (34.8% with epsilon4) and 103 AD patients (50.4% with epsilon4). Resting eyes-closed EEG data were recorded for all subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography. RESULTS: Results showed that amplitude of alpha 1 and 2 sources in occipital, temporal, and limbic areas was lower in subjects carrying the epsilon4 allele than in those not carrying the epsilon4 allele (p < 0.01). This was true for both MCI and AD. For the first time to our knowledge, a relationship was shown between ApoE genotype and global neurophysiological phenotype (ie, cortical alpha rhythmicity) in a preclinical AD condition, MCI, in addition to clinically manifest AD. INTERPRETATION: Such a demonstration motivates future genotype-EEG phenotype studies for the early prediction of AD conversion in individual MCI subjects.     

Sources of cortical rhythms in adults during physiological aging: a multicentric EEG study

This electroencephalographic (EEG) study tested whether cortical EEG rhythms (especially delta and alpha) show a progressive increasing or decreasing trend across physiological aging. To this aim, we analyzed the type of correlation (linear and nonlinear) between cortical EEG rhythms and age. Resting eyes-closed EEG data were recorded in 108 young (Nyoung; age range: 18-50 years, mean age 27.3+/-7.3 SD) and 107 elderly (Nold; age range: 51-85 years, mean age 67.3+/-9.2 SD) subjects. The EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Statistical results showed that delta sources in the occipital area had significantly less magnitude in Nold compared to Nyoung subjects. Similarly, alpha 1 and alpha 2 sources in the parietal, occipital, temporal, and limbic areas had significantly less magnitude in Nold compared to Nyoung subjects. These nine EEG sources were given as input for evaluating the type (linear, exponential, logarithmic, and power) of correlation with age. When subjects were considered as a single group there was a significant linear correlation of age with the magnitude of delta sources in the occipital area and of alpha 1 sources in occipital and limbic areas. The same was true for alpha 2 sources in the parietal, occipital, temporal, and limbic areas. In general, the EEG sources showing significant linear correlation with age also supported a nonlinear correlation with age. These results suggest that the occipital delta and posterior cortical alpha rhythms decrease in magnitude during physiological aging with both linear and nonlinear trends. In conclusion, this new methodological approach holds promise for the prediction of dementia in mild cognitive impairment by regional source rather than surface EEG data and by both linear and nonlinear predictors.     

Cortical sources of resting state electroencephalographic rhythms in Parkinson’s disease related dementia and Alzheimer’s disease

Objective

Here we test the hypothesis that cortical source mapping of resting state electroencephalographic (EEG) rhythms could characterize neurodegenerative disorders inducing cognitive impairment such as Parkinson’s disease related dementia (PDD) and Alzheimer’s disease (AD).

Methods

To address this issue, eyes-closed resting state EEG rhythms were recorded in 13 PDD, 20 AD, and 20 normal elderly (Nold) subjects. Age, gender, and education were carefully matched across the three groups. Mini Mental State Evaluation (MMSE) score probed subjects’ global cognitive status, and was matched between the PDD and AD groups. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha1 (8–10.5 Hz), alpha2 (10.5–13 Hz), beta1 (13–20 Hz), and beta2 (20–30 Hz). EEG cortical sources were estimated by low resolution brain electromagnetic source tomography (LORETA).

Results

With respect to the Nold and AD groups, the PPD group was characterized by peculiar abnormalities of central delta sources and posterior cortical sources of theta and beta1 rhythms. With respect to the Nold group, the PDD and AD groups mainly pointed to lower posterior cortical sources of alpha1 rhythms, which were positively correlated to MMSE score across all PDD and AD subjects as a whole (the lower the alpha sources, the lower the MMSE score). This alpha decrease was greater in the AD than PPD patients.

Conclusions

The results suggest that topography and frequency of eyes-closed resting state cortical EEG rhythms distinguished PDD and AD groups.

Significance

We report the existence of different effects of neurodegeneration on the cortical neural synchronization mechanisms generating resting state EEG rhythms in PDD and AD patients.     

Stability of clinical condition in mild cognitive impairment is related to cortical sources of alpha rhythms: an electroencephalographic study

Previous evidence has shown that resting eyes-closed cortical alpha rhythms are higher in amplitude in mild cognitive impairment (MCI) than Alzheimer's disease (AD) subjects (Babiloni et al. [2006a]: Human Brain Mapp 27:162-172; [2006b]: Clin Neurophysiol 117:252-268; [2006c]: Neuroimage 29:948-964; [2006d]: Ann Neurol 59:323-334; [2006e]: Clin Neurophysiol 117:1113-1129; [2006f]: Neuroimage 31:1650-1665). This study tested the hypothesis that, in amnesic MCI subjects, high amplitude of baseline cortical alpha rhythms is related to long-term stability of global cognition on clinical follow-up. Resting electroencephalographic (EEG) data were recorded in 100 amnesic MCI subjects during eyes-closed condition. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz). Cortical EEG sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Global cognition was indexed by mini mental state evaluation (MMSE) score at the time of EEG recordings (baseline) and about after 1 year. Based on the MMSE percentage difference between baseline and 1-year follow-up (MMSEvar), the MCI subjects were retrospectively divided into three arbitrary groups: DECREASED (MMSEvar ≤ -4%; N = 43), STABLE (MMSEvar ≈ 0; N = 27), and INCREASED (MMSEvar ≥ +4%; N = 30). Subjects' age, education, individual alpha frequency, gender, and MMSE scores were used as covariates for statistical analysis. Baseline posterior cortical sources of alpha 1 rhythms were higher in amplitude in the STABLE than in the DECREASED and INCREASED groups. These results suggest that preserved resting cortical neural synchronization at alpha frequency is related to a long-term (1 year) stable cognitive function in MCI subjects. Future studies should use serial MMSE measurements to confirm and refine the present results.     

Abnormal fronto-parietal coupling of brain rhythms in mild Alzheimer's disease: a multicentric EEG study

Cholinergic deafferentation/recovery in rats mainly impinges on the fronto‐parietal coupling of brain rhythms [D. P. Holschneider et al. (1999) Exp. Brain Res., 126 , 270–280]. Is this reflected by the functional coupling of fronto‐parietal cortical rhythms at an early stage of Alzheimer's disease (mild AD)? Resting electroencephalographic (EEG) rhythms were studied in 82 patients with mild AD and in control subjects, such as 41 normal elderly (Nold) subjects and 25 patients with vascular dementia (VaD). Patients with AD and VaD had similar mini‐mental state evaluation scores of 17–24. The functional coupling was estimated by means of the synchronization likelihood (SL) of the EEG data at electrode pairs, accounting for linear and non‐linear components of that coupling. Cortical rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha (1 8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), beta 2 (20–30 Hz) and gamma (30–40 Hz). A preliminary data analysis (Nold) showed that surface Laplacian transformation of the EEG data reduced the values of SL, possibly because of the reduction of influences due to head volume conduction. Therefore, the final analysis was performed on Laplacian‐transformed EEG data. The SL was dominant at alpha 1 band in all groups. Compared with the Nold subjects, patients with VaD and mild AD presented a marked reduction of SL at both fronto‐parietal (delta–alpha) and inter‐hemispherical (delta–beta) electrode pairs. The feature distinguishing the patients with mild AD with respect to patients with VaD groups was a more prominent reduction of fronto‐parietal alpha 1 SL. These results suggest that mild AD is characterized by an abnormal fronto‐parietal coupling of the dominant human cortical rhythm at 8–10.5 Hz.     

Hypercapnia affects the functional coupling of resting state electroencephalographic rhythms and cerebral haemodynamics in healthy elderly subjects and in patients with amnestic mild cognitive impairment

ObjectiveCerebral vasomotor reactivity (VMR) and coherence of resting state electroencephalographic (EEG) rhythms are impaired in Alzheimer’s disease (AD) patients. Here we tested the hypothesis that these two variables could be related.MethodsWe investigated VMR and coherence of resting state EEG rhythms in nine normal elderly (Nold) and in 10 amnesic mild cognitive impairment (MCI) subjects. Resting state eyes-closed EEG data were recorded at baseline pre-CO₂ (ambient air, 2 min), during 7% CO₂/air mixture inhalation (hypercapnia, 90 s) and post-CO₂ (ambient air, 2 min) conditions. Simultaneous frontal bilateral near-infrared spectroscopy (NIRS) was performed to assess VMR by cortical oxy- and deoxy-haemoglobin concentration changes. EEG coherence across all electrodes was computed at delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), beta 2 (20–30 Hz) and gamma (30–40 Hz) bands.ResultsIn Nold subjects, ‘total coherence’ of EEG across all frequency bands and electrode pairs decreased during hypercapnia, with full recovery during post-CO₂. Total coherence resulted lower in pre-CO₂ and post-CO₂ and presented poor reactivity during CO₂ inhalation in MCI patients compared with Nold subjects. Hypercapnia increased oxy-haemoglobin and decreased deoxy-haemoglobin concentrations in both groups. Furthermore, the extent of changes in these variables during CO₂ challenge was correlated with the EEG coherence, as a reflection of neurovascular coupling.ConclusionsHypercapnia induced normal frontal VMR that was detected by NIRS in both Nold and amnesic MCI groups, while it produced a reactivity of global functional coupling of resting state EEG rhythms only in the Nold group.SignificanceIn amnesic MCI patients, global EEG functional coupling is basically low in amplitude and does not react to hypercapnia.     

White‐matter lesions along the cholinergic tracts are related to cortical sources of EEG rhythms in amnesic mild cognitive impairment

Does impairment of cholinergic systems represent an important factor in the development of amnesic mild cognitive impairment (aMCI), as a preclinical stage of Alzheimer's disease (AD)? Here we tested the hypothesis that electroencephalographic (EEG) rhythms, known to be modulated by the cholinergic system, may be particularly affected in aMCI patients with lesions along the cholinergic white‐matter tracts. Eyes‐closed resting EEG data were recorded in 28 healthy elderly (Nold) and 57 aMCI patients. Lesions along the cholinergic white‐matter tracts were detected with fluid‐attenuated inversion recovery sequences on magnetic resonance imaging. The estimation of the cholinergic lesion was performed with a validated semi‐automatic algorithm pipeline after registration to a stereotactic template, image integration with stereotactic masks of the cholinergic tracts, and normalization to intracranial volume. The aMCI patients were divided into two groups of high (MCI Ch+; N = 29; MMSE = 26.2) and low cholinergic damage (MCI Ch?; N = 28; MMSE = 26.6). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). Cortical EEG generators were estimated by LORETA software. As main results, (i) power of occipital, parietal, temporal, and limbic alpha 1 sources was maximum in Nold, intermediate in MCI Ch?, and low in MCI Ch+ patients; (ii) the same trend was true in theta sources. These results are consistent with the hypothesis that damage to the cholinergic system is associated with alterations of EEG sources in aMCI subjects. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Ibuprofen treatment modifies cortical sources of EEG rhythms in mild Alzheimer’s disease

ObjectiveNon-steroidal anti-inflammatory drugs such as ibuprofen have a protective role on risk of Alzheimer’s disease (AD). Here we evaluated the hypothesis that long-term ibuprofen treatment affects cortical sources of resting electroencephalographic (EEG) rhythms in mild AD patients.MethodsTwenty-three AD patients (13 treated AD IBUPROFEN; 10 untreated AD PLACEBO) were enrolled. Resting EEG data were recorded before and 1 year after the ibuprofen/placebo treatment. EEG rhythms were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). LORETA was used for EEG source analysis.ResultsIn the AD PLACEBO group, amplitude of delta sources was globally greater at follow-up than baseline. Instead, amplitude of delta sources remained stable or decreased in the majority of the AD IBUPROFEN patients. Clinical (CDR) but not global cognitive status (MMSE) reflected EEG results.ConclusionsThese results suggest that in mild AD patients, a long-term ibuprofen treatment slightly slows down the progressive increment of delta rhythms as a sign of contrast against the neurodegenerative processes.SignificanceThey motivate future investigations with larger population and extended neuropsychological testing, to study the relationships among ibuprofen treatment, delta cortical sources, and higher order functions.     

White matter vascular lesions are related to parietal-to-frontal coupling of EEG rhythms in mild cognitive impairment

Do cerebrovascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI) as a putative preclinical stage of AD? Here we tested the hypothesis that directionality of fronto‐parietal functional coupling of electroencephalographic (EEG) rhythms is relatively preserved in amnesic MCI subjects in whom the cognitive decline is mainly explained by white‐matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold) and 78 amnesic MCI. In the MCI subjects, white‐matter vascular load was quantified based on magnetic resonance images (0–30 visual rating scale). EEG rhythms of interest were δ (2–4 Hz), θ (4–8 Hz), α1 (8–10.5 Hz), α2 (10.5–13 Hz), β1 (13–20 Hz), and β2 (20–30 Hz). Directionality of fronto‐parietal functional coupling of EEG rhythms was estimated by directed transfer function software. As main results, (i) fronto‐parietal functional coupling of EEG rhythms was higher in magnitude in the Nold than in the MCI subjects; (ii) more interestingly, that coupling was higher at θ, α1, α2, and β1 in MCI V+ (high vascular load; N = 42; MMSE = 26) than in MCI V? group (low vascular load; N = 36; MMSE= 26.7). These results are interpreted as supporting the additive model according to which MCI state would result from the combination of cerebrovascular and neurodegenerative lesions. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.     

Discrimination of Alzheimer's disease and mild cognitive impairment by equivalent EEG sources: a cross-sectional and longitudinal study.

OBJECTIVES: The spatial aspects of brain electrical activity can be assessed by equivalent EEG frequency band generators. We aimed to describe alterations of these EEG generators in Alzheimer's disease (AD) and healthy aging and whether they could serve as predictive markers of AD in subjects at risk. METHODS: The amplitude and 3-dimensional localization of equivalent EEG sources were evaluated using FFT dipole approximation in 38 mild AD patients, 31 subjects with mild cognitive impairment (MCI) and 24 healthy control subjects. RESULTS: AD patients showed an increase of delta and theta global field power (GFP), which corresponds to the generalized EEG amplitude, as well as a reduction of alpha GFP when compared to the controls. A decrease of alpha and beta GFP was found in AD patients, as compared to the MCI subjects. With respect to topography in the antero-posterior direction, sources of alpha and beta activity shifted more anteriorly in AD patients compared to both the controls and MCI subjects. No significant difference was found between MCI and controls. Combined alpha and theta GFP were the best discriminating variables between AD patients and controls (84% correct classification) and AD and MCI subjects (78% correctly classified). MCI subjects were followed longitudinally (25 months on average) in order to compare differences in baseline EEG variables between MCI subjects who progressed to AD (PMCI) and those who remained stable (SMCI). Compared to SMCI, PMCI had decreased alpha GFP and a more anterior localization of sources of theta, alpha and beta frequency. In a linear discriminant analysis applied on baseline values of the two MCI subgroups, the best predictor of future development of AD was found to be antero-posterior localization of alpha frequency. CONCLUSIONS: FFT dipole approximation and frequency analysis performed by conventional FFT showed comparable classification accuracy between the studied groups. We conclude that localization and amplitude of equivalent EEG sources could be promising markers of early AD.     

Resting state cortical rhythms in athletes: A high-resolution EEG study

The present electroencephalographic (EEG) study tested the working hypothesis that the amplitude of resting state cortical EEG rhythms (especially alpha, 8-12 Hz) was higher in elite athletes compared with amateur athletes and non-athletes, as a reflection of the efficiency of underlying back-ground neural synchronization mechanisms. Eyes closed resting state EEG data were recorded in 16 elite karate athletes, 20 amateur karate athletes, and 25 non-athletes. The EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Statistical results showed that the amplitude of parietal and occipital alpha 1 sources was significantly higher in the elite karate athletes than in the non-athletes and karate amateur athletes. Similar results were observed in parietal and occipital delta sources as well as in occipital theta sources. Finally, a control confirmatory experiment showed that the amplitude of parietal and occipital delta and alpha 1 sources was stronger in 8 elite rhythmic gymnasts compared with 14 non-athletes. These results supported the hypothesis that cortical neural synchronization at the basis of eyes-closed resting state EEG rhythms is enhanced in elite athletes than in control subjects.     

Cortical sources of EEG rhythms are abnormal in down syndrome

ObjectivePrevious studies have been inconclusive whether dominant resting state alpha rhythms are greater or lower in amplitude in subjects with Down syndrome (DS) when compared to control subjects, ample resting alpha rhythms being considered as a reflection of good mechanisms of cortical neural synchronization. Here we tested the hypothesis that when the effects of head volume conduction are taken into account by the normalization of the cortical sources of resting alpha rhythms, these sources are lower in amplitude in DS subjects than in controls in line with typical findings in Alzheimer’s disease patients.MethodsEyes-closed resting electroencephalographic (EEG) data were recorded in 45 DS subjects (25 males; mean age of 22.8 years ± 0.7 standard error of mean (SEM)) and in 45 age-matched cognitively normal subjects (25 males; mean age of 22.4 years ± 0.5 SEM). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), beta 2 (20–30 Hz), and gamma (30–40 Hz). Cortical EEG sources were estimated by low resolution electromagnetic tomography (LORETA) and normalized across all voxels and frequencies.ResultsCentral, parietal, occipital, and temporal cortical sources of resting alpha and beta rhythms were lower in amplitude in the DS than control subjects, whereas the opposite was true for occipital delta cortical sources. A control analysis on absolute source values showed that they were globally larger in amplitude across several frequency bands in DS than control subjects.ConclusionsThese results suggest that normalized cortical sources of alpha rhythms are lower in amplitude in DS than control subjects, as it is typically found in Alzheimer’s disease.SignificanceDS is accompanied by a functional impairment of cortical neuronal synchronization mechanisms in the resting state condition.